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Canadian Journal of Cardiology

Association Between Circulating Oxidized LDL and Atherosclerotic Cardiovascular Disease: A Meta-analysis of Observational Studies

  • Shen Gao
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Dong Zhao
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Miao Wang
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Fan Zhao
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Xueyu Han
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Yue Qi
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
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  • Jing Liu
    Correspondence
    Corresponding author: Dr Jing Liu, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No 2 Anzhen St, Chaoyang District, Beijing, China. Tel.: +86-010-64456710; fax: +86-010-64219738.
    Affiliations
    Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
    Search for articles by this author

      Abstract

      Background

      Although basic research has suggested that oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis, population observational studies have yielded conflicting results about the association between circulating ox-LDL and atherosclerotic cardiovascular disease (ASCVD). Therefore, we performed a systematic review and meta-analysis of currently available observational studies to verify the association between circulating ox-LDL and ASCVD.

      Methods

      We systematically searched PubMed and the Cochrane Library from their inception to March 27, 2017, for nested case-control studies, case-cohort studies, and prospective cohort studies on the relationship between ox-LDL and ASCVD. Studies that did not assess the hazard ratio, relative risk, or odds ratio of ox-LDL or did not adjust for other risk factors, or those without examination of ox-LDL before collection of ASCVD occurrences were excluded. The summarized effect size was combined using fixed effect models. Subgroup analyses were performed on the basis of study quality, study design, definition of ASCVD events, effect size types, types of ox-LDL assay, ox-LDL contrast level, and whether low-density lipoprotein cholesterol was adjusted in a multivariate model.

      Results

      A total of 12 included studies consisted of 3 nested case-control studies, 1 case-cohort study, 5 hospital-based cohort studies, and 3 community-based cohort studies. The summary effect size of increased circulating ox-LDL was 1.79 (95% confidence interval, 1.56-2.05) for ASCVD. Similar associations were shown in all subgroups.

      Conclusions

      Our findings indicate that increased levels of circulating ox-LDL are associated with clinical ASCVD events. Further well designed community-based cohort studies or intervention studies are needed to confirm our findings.

      Résumé

      Contexte

      Même si la recherche fondamentale suggère que les lipoprotéines de faible densité (LDL) oxydées jouent un rôle dans la pathogenèse de l’athérosclérose, des études observationnelles de population ont abouti à des résultats contradictoires en ce qui concerne le lien entre les LDL oxydées circulantes et les maladies cardiovasculaires (MCV) athéroscléreuses. C’est pourquoi nous avons effectué une revue et une méta-analyse systématiques des études observationnelles disponibles à ce jour pour vérifier le lien entre les LDL oxydées circulantes et les MCV athéroscléreuses.

      Méthodologie

      Nous avons réalisé une recherche systématique dans PubMed et la bibliothèque Cochrane à partir du moment de leur création jusqu’au 27 mars 2017, et ce, afin de trouver des études de cas-témoins emboîtés, des études cas-cohortes et des études de cohortes prospectives évaluant le lien entre les LDL oxydées circulantes et les MCV athéroscléreuses. Les études suivantes ont été exclues : celles qui n’ont pas évalué le rapport des risques instantanés, le risque relatif ou le rapport de cotes relativement aux LDL oxydées; celles qui n’ont pas ajusté les résultats en fonction d’autres facteurs de risque; ou celles qui n’ont pas évalué le taux de LDL oxydées avant de relever la survenue de manifestations attribuables aux MCV athéroscléreuses. L’ampleur globale de l’effet a été obtenue en utilisant des modèles à effets fixes. Des analyses de sous-groupes ont été réalisées en se basant sur la qualité de l’étude, la méthodologie, la définition des manifestations attribuables aux MCV athéroscléreuses, le type d’ampleur de l’effet, le type d’analyses pour mesurer le taux de LDL oxydées, le niveau de contraste lié aux LDL oxydées, et si le taux de cholestérol LDL a été ajusté selon un modèle multivarié.

      Résultats

      Au total, 12 études ont été prises en compte, soit 3 études de cas-témoins emboîtés, 1 étude cas-cohortes, 5 études de cohortes hospitalières et 3 études de cohortes communautaires. L’ampleur de l’effet globale de l’augmentation des LDL oxydées dans le sang était de 1,79 (intervalle de confiance à 95 % : 1,56-2,05) pour les MCV athéroscléreuses. Un lien similaire a été observé dans tous les sous-groupes.

      Conclusion

      Nos résultats montrent qu’un taux circulant élevé de LDL oxydées est associé à des manifestations cliniques attribuables aux MCV athéroscléreuses. D’autres études de cohortes communautaires ou études d’intervention bien conçues seront nécessaires pour confirmer nos résultats.
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